Chemotherapy has developed to an increasingly effective line of defense against cancer (1). In glioblastoma (GBM), the alkylating agent temozolomide (TMZ) has become a standard, in combination with surgical resection and radiotherapy. There is nevertheless a considerable need to develop alternative treatment options, as GBM remains a fatal disease with a median overall survival of only 15 months (2, 3). For anticancer drug discovery, two major strategies are traditionally employed (4). One is the targeted approach where cancer-related molecules and/or signaling cascades need to be exposed before specific compounds can be designed for distinct interference and inhibition. Alternatively, empirical screening of hundreds to thousands of compounds can be conducted to identify otherwise unpredictable antineoplastic effects. Both strategies, however, are burdened with high attrition rates during clinical translation (5, 6). This may in part be caused by the use of inept cellular model systems for drug evaluation at early developmental stages (7), e.g. inter- and intra-patient tumor heterogeneity is rarely reflected within these systems. The present inventors have developed an in vitro cellular system that is closely mirroring GBM in vivo and is, thus, particular suitable to identify compounds and combinations of compounds that are likely to also provide GBM specific anticancer activity when used in vivo. Using this in vitro cellular system the present inventors were able to identify compounds and compound combinations for the improved chemotherapy of glioblastoma.